Michael Grunze, Institute for Molecular Biophysics, University of Maine, and Lehrstuhl für Angewandte Physikalische Chemie, Universität Heidelberg, Germany Both the elemental and molecular structure sensitivity of established surface spectroscopic techniques are of great value in the development and failure analysis of biomedical devices. However, analysis is –by necessity- done ex situ, so the question always remains if the conclusions derived from the data are representative of the system in a physiological environment. Significant technical complications in carrying out the experiments and in data interpretation are encountered when spectroscopy is done in situ, for example in Vibrational Sum Frequency Generation, Infrared Microscopy, or X-ray absorption- and emission spectroscopy using synchrotron radiation. In general, the problem turns out to be far more complicated than anticipated by any physical scientist. If at all, only simplified model systems of biomedical relevance are presently amenable to in situ surface spectroscopy experiments. However, their detailed analysis, combined with the knowledge derived from biological and medical experiments, can in some cases lead to a better understanding of biomedical processes. This talk will discuss both success and failures; I will discuss examples of failure analysis and failure (limitations) of the application of biological surface science in experimental systems. Examples will also be presented that will demonstrate the significant contributions of Biological Interface Science in providing new insights into biological and biomedical problems.